Ovarian Cancer: Testing for BRCA Mutations

Bradley J. Monk, MD, FACOG, FACS:So, I’d like to discuss a case with you, a typical scenario, a woman unfortunately diagnosed with an advanced ovarian cancer, now over 3 years ago. She presented when she was 40 years old, which is unusually young. The median age of advanced ovarian cancer is in the mid-50s. This woman was 40, and she had no past medical or surgical history except that her mother had breast cancer, and she went to her doctor with some abdominal complaints, which led to a sequence of diagnostic events including an ultrasound, a CT scan, and a CA-125. And, unfortunately, the ultrasound showed a mass. Ultrasonographically, we can pretty much tell benign from malignant masses. This mass was solid. Solid masses are more likely to be malignant. The CT scan showed intraperitoneal disease, which we call carcinomatosis, and the CA-125 was just under 1000. So, the chance of this being an ovarian cancer is virtually 100%. However, in the interim between the time that the patient was seen by her primary care physician and the gynecologic oncologist, a biopsy was performed and showed a high-grade serous cancer.

So, the first point is that we don’t have screening for ovarian cancer, but every patient should be referred to a gynecologic oncologist to be evaluated for the opportunity to do a surgery, with the goal of the surgery being complete resection. We used to say that optimal cytoreduction was less than a centimeter. It’s not. There’s nothing optimal about leaving cancer behind. She was evaluated by a gynecologic oncologist. The goal was clear, complete resection, all macroscopic disease. She had a vertical laparotomy incision, a hysterectomy, omentectomy, and debulking operation. Now, unfortunately, there was some residual disease left behind, so maybe one could have argued that they should have started with neoadjuvant chemotherapy. I get it, it’s a hard decision. They decided to go for it. They did an operation. She recovered well and then was considered for adjuvant therapy.

And, at that time in 2014, we had a fascination with intraperitoneal chemotherapy. Quite frankly, we don’t anymore. We now have a recent trial not yet published, GOG 252, that showed that intraperitoneal chemotherapy is not valid. In the olden days, we were engaged by aNew England Journal of Medicinepaper that looked at intraperitoneal chemotherapy, but it also was dose intense and weekly. So, it didn’t just ask 1 question. She was treated with intraperitoneal chemotherapy and did well. And as per the guidelines from the American Society of Clinical Oncology, the Society of Gynecologic Oncology, and the National Comprehensive Cancer Network—ASCO, SGO, and NCCN—she was tested forBRCAgermline mutations. And I get it, her mother had breast cancer, she was young, but age and family history are not enough to determine which patient should be tested for a germline mutation. All patients should be tested, and indeed she was, and she had a germlineBRCAmutation. And germlineBRCA-mutated ovarian cancers respond exquisitely well because that’s whatBRCAdoes. It repairs double-stranded DNA breaks, and that’s what platinum does, it breaks the DNA. So, she couldn’t repair the double-stranded platinum-induced breaks, had a complete response, and did well.

Transcript edited for clarity.

Platinum-Sensitive Recurrent Ovarian Cancer

September 2014

• A 40-year old Caucasian female presented to her gynecologist with abdominal pain and increased urinary urgency and frequency
  • PMH: unremarkable
  • FH: mother died of breast cancer at age 46
  • PE: tenderness in abdominal right lower quadrant; shifting dullness on abdominal palpation and percussion
  • Ultrasound: Abdominal and pelvic ultrasound showed a right-sided solid pelvic mass and ascites
• The patient was then referred to a gynecologic oncologist
  • Genetic testing was positive for BRCA1 mutation
  • Abdominal/pelvic CT findings showed a 5-cm x 2.5 cm x 3-cm right pelvic mass; ascites and omental cake was noted
  • CA125, 998 U/mL
• Biopsy findings showed stage 3C epithelial ovarian cancer
• Hysterectomy, bilateral salpingo-oophorectomy, and omentectomy was performed and optimal debulking was achieved (residual disease <1 cm)
• Treatment was initiated with IV/IP carboplatin/paclitaxel
  • After 6 cycles of therapy, CA-125 level declined to 9.3 U/ml.
  • Chemotherapy was tolerated well and without any unexpected toxicities

November 2016

• The patient reported feeling bloated and exhausted
• CT scan confirmed disease recurrence with ascites
• She was treated with carboplatin/paclitaxel/bevacizumab for 6 cycles and had a good response to therapy
• Following completion, she was continued on maintenance bevacizumab
• She continued to show improved response

January 2018

• The patient reported back with complaints of weight loss and abdominal distension
• CT scan revealed presence of small diffuse intraperitoneal masses